Chronic Lymphocytic LeukemiaPhase 2/3ULTRA-VNCT03801525
Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)
A Phase 2/3 study testing Ublituximab, Umbralisib and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by TG Therapeutics, Inc. at 50 sites in United States.
Trial summary
ULTRA-V: Study to Assess the Efficacy and Safety of Ublituximab in Combination with Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects with Chronic Lymphocytic Leukemia (CLL) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- Ublituximab, Umbralisib and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 277 participants
- Where
- 50 sitesUnited States
- Study dates
- 16 May 2019to 20 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that warrants treatment
- Adequate organ system function as specified in the protocol
- Ability to follow protocol procedures.
Who cannot join
- Subjects receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1
- Prior exposure to any PI3K inhibitor or venetoclax
- Autologous hematologic stem cell transplant within 6 months of study entry. Prior allogeneic hematologic stem cell transplant is excluded
- Active Hepatitis B or Hepatitis C.
Trial locations and contacts
50 sites in 1 country.
50 sites in 1 country
United States50 sites
TG Therapeutics Investigational Trial Site
Ann Arbor, Michigan, 48197
TG Therapeutics Investigational Trial Site
Atlanta, Georgia, 30322
TG Therapeutics Investigational Trial Site
Aurora, Colorado, 80012
TG Therapeutics Investigational Trial Site
Austin, Texas, 78705
TG Therapeutics Investigational Trial Site
Bethesda, Maryland, 37210
TG Therapeutics Investigational Trial Site
Birmingham, Alabama, 35294
TG Therapeutics Investigational Trial Site
Blacksburg, Virginia, 24060
TG Therapeutics Investigational Trial Site
Boca Raton, Florida, 33486
TG Therapeutics Investigational Trial Site
Charleston, South Carolina, 29414
TG Therapeutics Investigational Trial Site
Charlotte, North Carolina, 28204
TG Therapeutics Investigational Trial Site
Chattanooga, Tennessee, 37404
TG Therapeutics Investigational Trial Site
Columbia, Maryland, 21044
TG Therapeutics Investigational Trial Site
Columbus, Ohio, 43210
TG Therapeutics Investigational Trial Site
Decatur, Illinois, 62526
TG Therapeutics Investigational Trial Site
Des Moines, Iowa, 50309
TG Therapeutics Investigational Trial Site
Detroit, Michigan, 48201
TG Therapeutics Investigational Trial Site
Detroit, Michigan, 48202
TG Therapeutics Investigational Trial Site
Duarte, California, 91010
TG Therapeutics Investigational Trial Site
Eugene, Oregon, 97401
TG Therapeutics Investigational Trial Site
Fort Myers, Florida, 33901
TG Therapeutics Investigational Trial Site
Fort Wayne, Indiana, 46804
TG Therapeutics Investigational Trial Site
Gainesville, Virginia, 20155
TG Therapeutics Investigational Trial Site
Greenville, South Carolina, 29616
TG Therapeutics Investigational Trial Site
Hackensack, New Jersey, 07601
TG Therapeutics Investigational Trial Site
Huntsville, Alabama, 35805
TG Therapeutics Investigational Trial Site
Indianapolis, Indiana, 46237
TG Therapeutics Investigational Trial Site
Jacksonville, Florida, 32224
TG Therapeutics Investigational Trial Site
Knoxville, Tennessee, 37916
TG Therapeutics Investigational Trial Site
La Jolla, California, 92093
TG Therapeutics Investigational Trial Site
Lebanon, New Hampshire, 03756
TG Therapeutics Investigational Site
Louisville, Kentucky, 40207
TG Therapeutics Investigational Trial Site
Morristown, New Jersey, 07960
TG Therapeutics Investigational Trial Site
Nashville, Tennessee, 37203
TG Therapeutics Investigational Trial Site
New York, New York, 10065
TG Therapeutics Investigational Trial Site
Niles, Illinois, 60714
TG Therapeutics Investigational Trial Site
Ogden, Utah, 84405
TG Therapeutics Investigational Trial Site
Omaha, Nebraska, 68198
TG Therapeutics Investigational Site
Peoria, Illinois, 61615
TG Therapeutics Investigational Trial Site
Philadelphia, Pennsylvania, 19106
TG Therapeutics Investigational Trial Site
Rochester, Minnesota, 55905
TG Therapeutics Investigational Trial Site
Salt Lake City, Utah, 84106
TG Therapeutics Investigational Trial Site
San Antonio, Texas, 78229
TG Therapeutics Investigational Trial Site
Seattle, Washington, 98104
TG Therapeutics Investigational Trial Site
Seattle, Washington, 98108
TG Therapeutics Investigational Trial Site
St. Petersburg, Florida, 33705
TG Therapeutics Investigational Trial Site
Stamford, Connecticut, 06904
TG Therapeutics Investigational Trial Site
Tampa, Florida, 33612
TG Therapeutics Investigational Trial Site
Tucson, Arizona, 85711
TG Therapeutics Investigational Trial Site
Tyler, Texas, 75702
TG Therapeutics Investigational Trial Site
Westwood, Kansas, 66210
About this study
Official title: Phase 2/3 Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects With Chronic Lymphocytic Leukemia (CLL)
ULTRA-V: Study to Assess the Efficacy and Safety of Ublituximab in Combination with Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects with Chronic Lymphocytic Leukemia (CLL)
Read the detailed description
This is an open-label, multicenter, Phase 2/3 study to evaluate the efficacy and safety of the combination of ublituximab + umbralisib + venetoclax (U2-V) compared to the combination of ublituximab + umbralisib (U2) in participants with either treatment naïve or previously treated CLL/ small lymphocytic lymphoma (SLL).
- Being tested
- Ublituximab, Umbralisib, Venetoclax
- Keywords
- CLL, SLL
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UblituximabDrug
Also called TG-1101
- recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody
- administered as an IV infusion
UmbralisibDrug
Also called TGR-1202, UKONIQ
- inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e)
- Tablet form
VenetoclaxDrug
Also called Venclexta®
- B-cell lymphoma 2 (BCL-2) inhibitor
- Tablet form
| Study group | Role | What they receive |
|---|---|---|
| Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V) | Experimental | Participants were administered ublituximab, 150 milligrams (mg), intravenous (IV) infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6; umbralisib, 800 mg, oral tablet, once daily (QD) through Cycles 1-24; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-24. MRD positive participants were administered umbralisib, 800 mg, oral tablet, QD, on Days 1-28 from Cycle 25 onwards (1 Cycle = 28 days), until disease progression, unacceptable toxicity, or withdrawal from the study. Receives: Drug: Ublituximab; Drug: Umbralisib; Drug: Venetoclax |
| Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V) | Experimental | Participants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, 9,12, and 15; umbralisib, 800 mg, oral tablet, QD through Cycles 1-15; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-15 (1 Cycle = 28 days). Receives: Drug: Ublituximab; Drug: Umbralisib; Drug: Venetoclax |
| Phase 3: Ublituximab + Umbralisib (U2) | Experimental | Participants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, then every three cycles along with umbralisib, 800 mg, oral tablet, QD (1 Cycle = 28 days) from Cycle 1 until disease progression, unacceptable toxicity, or withdrawal from the study. Receives: Drug: Ublituximab; Drug: Umbralisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 2: Complete Response (CR) Rate as Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Criteria
CR rate=percent of participants who achieved CR or complete response with incomplete marrow recovery(CRi).CR=no evidence of new disease,absolute lymphocyte count(ALC) in peripheral blood<4x10^9 per liter(/L),regression of nodal masses to normal size <1.5 centimeters(cm) in longest diameter(LD),normal spleen and liver size,no constitutional symptoms,cytological/pathological evaluation of bone marrow(BM) smear/biopsy must be at least normocellular for age without evidence for typical chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma(SLL) lymphocytes by morphological criteria,peripheral blood counts with absolute neutrophil count(ANC)≥1.5x10^9/L or platelet≥100x10^9/L or hemoglobin≥110 grams per liter(g/L) without red blood cell(RBC) transfusions,all without need for exogenous growth factors.CRi=all CR criteria but with persistent anemia,thrombocytopenia,or neutropenia or hypocellular BM that is related to prior/ongoing drug toxicity(and not to CLL/SLL).
Measured: Up to 43.2 months
Phase 2: Overall Response Rate (ORR) Per iwCLL 2018 Criteria
ORR=percent of participants who achieve CR,CRi,partial response(PR) or PR with lymphocytosis(PR-L).CR=no evidence of new disease;ALC<4x10^9/L;regression of nodal masses to<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10^9/L,platelet≥100x10^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline(BL) in ALC(or decrease to<4x10^9/L) or sum of products(SPD) of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive progressive disease(PD);platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.
Measured: Up to 43.2 months
Phase 3: Progression-Free Survival (PFS) Per iwCLL 2018 Criteria
PFS was assessed in participants treated with U2-V compared with U2. PFS was defined as the interval between randomization and the date of definitive PD (as confirmed by the IRC) or death due to any cause, whichever occurs first. Participants who had no event (progression or death) were censored at the day of their last adequate disease assessment. PD= appearance of new nodes >1.5 cm in the LD, >50% increase in greatest diameter, new or recurrent hepatomegaly or splenomegaly, new unequivocal extra-nodal lesion, new non-target disease, ≥50% increase from the nadir in the sum of products of diameters (SPD) of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb.
Measured: Up to 43.2 months
Secondary outcomes (7)
Minimal Residual Disease (MRD) Negativity Rate
The MRD negativity rate was defined as the percentage of participants who achieved MRD negative status post-baseline, defined as a quantitative detection of less than one CLL/SLL cell in 10000 leukocytes by flow cytometry (MRD level, 10^-4) in blood or bone marrow (BM). If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow. Participants who did not have an MRD assessment at any post-baseline visits were considered non-responders and were included in the denominator when calculating MRD negativity rate.
Measured: Up to 43.2 months
Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related.
Measured: Up to 43.2 months
Phase 2: Time to Response (TTR) Per iwCLL 2018 Criteria
TTR was defined as the interval from enrollment to first documentation of CR, CRi, PR, or PR-L. TTR was analyzed via Kaplan-Meier method. CR=no evidence of new disease; ALC<4x10^9/L; regression of nodal masses to <1.5cm LD; normal spleen ,liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC≥1.5x10^9/L, platelet≥100x10^9/L, Hb≥110g/L. CRi=CR criteria but with persistent anemia, thrombocytopenia, or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from BL in ALC (or decrease to<4x10^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/B-lymphoid; no target, splenic, liver, or non-target disease with worsening that meets criteria for definitive PD; platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.
Measured: Up to 43.2 months
Phase 2: Duration of Response (DOR) Per iwCLL 2018 Criteria
DOR=interval from 1st documentation of CR,CRi,PR or PR-L to earlier of 1st documentation of definitive PD or death from any cause.CR=no evidence of new disease;ALC<4x10^9/L;regression of nodal masses to<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10^9/L,platelet≥100x10^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from BL in ALC(or decrease to<4x10^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive PD;platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria;not≥50% decrease from BL in ALC/decrease to<4x10^9/L.PD=evidence of new disease per protocol-specififed criteria.
Measured: Up to 43.2 months
Phase 3: CR Rate as Assessed by an Independent Review Committee (IRC) Per iwCLL 2018 Criteria
CR rate=percent of participants who achieved CR or CRi. CR=no evidence of new disease; ALC<4x10^9/L; regression of nodal masses to <1.5 cm LD; normal spleen, liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC ≥1.5x10^9/L, platelet ≥100x10^9/L, Hb ≥110g/L. CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity. CR assessment was subject to independent confirmation by the IRC in participants enrolled to the Phase 3 stage of the study.
Measured: Up to 43.2 months
Phase 3: ORR as Assessed by IRC Per iwCLL 2018 Criteria
ORR=percent of participants who achieve CR, CRi, PR or PR-L.CR=no evidence of new disease; ALC<4x10^9/L; regression of nodal masses to<1.5cm LD; normal spleen and liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC≥1.5x10^9/L, platelet≥100x10^9/L, Hb≥110g/L. CRi=CR criteria but with persistent anemia, thrombocytopenia, or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline (BL) in ALC (or decrease to<4x10^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/B-lymphoid; no target, splenic, liver, or non-target disease with worsening that meets criteria for definitive PD; platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.
Measured: Up to 43.2 months
Phase 3: Overall Survival (OS)
Overall Survival (OS) was defined as the interval from randomization to death from any cause. OS data was censored at the last documented date that the participant was confirmed alive for participants who withdrew consent or were lost to follow-up prior to the end of the study, and for participants whose vital status in the study could not be determined.
Measured: Up to 43.2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start16 May 2019
- Primary completion20 Dec 2022
- Study completion20 Dec 2022
Why it stopped: Strategic/Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by TG Therapeutics, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 277 participants (actual)
Sponsor and investigators
- Lead sponsor
- TG Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801525
- Sponsor's protocol ID
- U2-VEN-207
- Acronym
- ULTRA-V
- Status last verified
- Apr 2024
- First submitted
- 9 Jan 2019
- Last updated
- 19 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2/3 Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects With Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT03801525
- Acronym / sponsor ID
- ULTRA-V / U2-VEN-207
- Keywords
- CLL, SLL
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic/Business decision
- Enrolment
- 277 participants (actual)
- Lead sponsor
- TG Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 16 May 2019 (actual)
- Primary completion
- 20 Dec 2022 (actual)
- Study completion
- 20 Dec 2022 (actual)
- First posted
- 11 Jan 2019 (actual)
- Results
- Posted 19 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
ULTRA-V: Study to Assess the Efficacy and Safety of Ublituximab in Combination with Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects with Chronic Lymphocytic Leukemia (CLL)
Detailed description
This is an open-label, multicenter, Phase 2/3 study to evaluate the efficacy and safety of the combination of ublituximab + umbralisib + venetoclax (U2-V) compared to the combination of ublituximab + umbralisib (U2) in participants with either treatment naïve or previously treated CLL/ small lymphocytic lymphoma (SLL).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V) | Experimental | Drug: Ublituximab, Drug: Umbralisib, Drug: VenetoclaxParticipants were administered ublituximab, 150 milligrams (mg), intravenous (IV) infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6; umbralisib, 800 mg, oral tablet, once daily (QD) through Cycles 1-24; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-24. MRD positive participants were administered umbralisib, 800 mg, oral tablet, QD, on Days 1-28 from Cycle 25 onwards (1 Cycle = 28 days), until disease progression, unacceptable toxicity, or withdrawal from the study. |
| Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V) | Experimental | Drug: Ublituximab, Drug: Umbralisib, Drug: VenetoclaxParticipants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, 9,12, and 15; umbralisib, 800 mg, oral tablet, QD through Cycles 1-15; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-15 (1 Cycle = 28 days). |
| Phase 3: Ublituximab + Umbralisib (U2) | Experimental | Drug: Ublituximab, Drug: UmbralisibParticipants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, then every three cycles along with umbralisib, 800 mg, oral tablet, QD (1 Cycle = 28 days) from Cycle 1 until disease progression, unacceptable toxicity, or withdrawal from the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that warrants treatment
- Adequate organ system function as specified in the protocol
- Ability to follow protocol procedures.
Key exclusion criteria (4 listed)
- Subjects receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1
- Prior exposure to any PI3K inhibitor or venetoclax
- Autologous hematologic stem cell transplant within 6 months of study entry. Prior allogeneic hematologic stem cell transplant is excluded
- Active Hepatitis B or Hepatitis C.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UblituximabAlso: TG-1101* recombinant chimeric anti-CD20 (cluster of differentiation 20) monoclonal antibody * administered as an IV infusion | Drug | Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V), Phase 3: Ublituximab + Umbralisib (U2), Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V) |
| UmbralisibAlso: TGR-1202, UKONIQ* inhibitor of phosphoinositide 3-kinase (PI3K) delta and casein kinase 1 epsilon (CK1e) * Tablet form | Drug | Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V), Phase 3: Ublituximab + Umbralisib (U2), Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V) |
| VenetoclaxAlso: Venclexta®* B-cell lymphoma 2 (BCL-2) inhibitor * Tablet form | Drug | Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V), Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V) |
Primary outcome
Phase 2: Complete Response (CR) Rate as Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Criteria
Time frame: Up to 43.2 months
CR rate=percent of participants who achieved CR or complete response with incomplete marrow recovery(CRi).CR=no evidence of new disease,absolute lymphocyte count(ALC) in peripheral blood<4x10^9 per liter(/L),regression of nodal masses to normal size <1.5 centimeters(cm) in longest diameter(LD),normal spleen and liver size,no constitutional symptoms,cytological/pathological evaluation of bone marrow(BM) smear/biopsy must be at least normocellular for age without evidence for typical chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma(SLL) lymphocytes by morphological criteria,peripheral blood counts with absolute neutrophil count(ANC)≥1.5x10^9/L or platelet≥100x10^9/L or hemoglobin≥110 grams per liter(g/L) without red blood cell(RBC) transfusions,all without need for exogenous growth factors.CRi=all CR criteria but with persistent anemia,thrombocytopenia,or neutropenia or hypocellular BM that is related to prior/ongoing drug toxicity(and not to CLL/SLL).
Phase 2: Overall Response Rate (ORR) Per iwCLL 2018 Criteria
Time frame: Up to 43.2 months
ORR=percent of participants who achieve CR,CRi,partial response(PR) or PR with lymphocytosis(PR-L).CR=no evidence of new disease;ALC<4x10^9/L;regression of nodal masses to<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10^9/L,platelet≥100x10^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline(BL) in ALC(or decrease to<4x10^9/L) or sum of products(SPD) of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive progressive disease(PD);platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.
Phase 3: Progression-Free Survival (PFS) Per iwCLL 2018 Criteria
Time frame: Up to 43.2 months
PFS was assessed in participants treated with U2-V compared with U2. PFS was defined as the interval between randomization and the date of definitive PD (as confirmed by the IRC) or death due to any cause, whichever occurs first. Participants who had no event (progression or death) were censored at the day of their last adequate disease assessment. PD= appearance of new nodes >1.5 cm in the LD, >50% increase in greatest diameter, new or recurrent hepatomegaly or splenomegaly, new unequivocal extra-nodal lesion, new non-target disease, ≥50% increase from the nadir in the sum of products of diameters (SPD) of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb.
7 secondary outcomes
Minimal Residual Disease (MRD) Negativity Rate
Time frame: Up to 43.2 months
Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: Up to 43.2 months
Phase 2: Time to Response (TTR) Per iwCLL 2018 Criteria
Time frame: Up to 43.2 months
Phase 2: Duration of Response (DOR) Per iwCLL 2018 Criteria
Time frame: Up to 43.2 months
Phase 3: CR Rate as Assessed by an Independent Review Committee (IRC) Per iwCLL 2018 Criteria
Time frame: Up to 43.2 months
Phase 3: ORR as Assessed by IRC Per iwCLL 2018 Criteria
Time frame: Up to 43.2 months
Phase 3: Overall Survival (OS)
Time frame: Up to 43.2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
50 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ublituximab, Umbralisib and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by TG Therapeutics, Inc. at 50 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 2: Complete Response (CR) Rate as Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Criteria (time frame: Up to 43.2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.